Rapid testing of a sample for an analyte, such as a biomarker, or the testing of molecular interaction in a sample is increasingly in demand, especially in the field of personal medicine. Traditionally, diagnostic tests, such as immunoassays, require both incubation time and complicated devices for reading the assay. Immunoassays also often require significant preparation of a sample holder or chip for binding an analyte to a surface. Recently, Back-Scattering Interferometry (BSI) has been validated for biochemical assays to measure the rate, concentration, and affinity of biomolecular interactions, such as protein-protein, antibody-antigen interactions, small molecule-protein interactions, DNA-DNA and DNA-protein binding. BSI devices and methods are described, for example, in U.S. Pat. Nos. 6,381,925; 6,381,025; 6,809,828 and 7,130,060; international applications WO 2004/023115, WO 2006/047408 and WO 2008/144496; and U.S. patent publication U.S. 2006-0012800.
Back Scattering Interferometry also has advantages of only requiring a small sample, such as 1 microliter, to conduct a biological assay. BSI can also offer label-free detection in a micro-chip format with picomolar sensitivity. BSI can be particularly valuable where trace sample requirements, extraordinary sensitivity, and/or free-solution analysis is required. Unlike other assays and biosensor techniques, BSI does not require significant knowledge of the interacting species and eliminates the need for finessing surface attachment chemistries. In addition to providing insight into basic cellular function, BSI has demonstrated potential to facilitate the development of therapeutics and diagnostics. Moreover, BSI can serve as the platform for many research, clinical diagnostic, and pharmacogenomic assays.
One of the shortcomings of many current BSI devices and methods is maintaining the temperature of the sample while it is being examined, while also maintaining the temperature of the device. A small change in temperature of the sample or the device can cause a change in a refractive index, which can lead to errors or non-specific measurements by an interferometer. It would be desirable in the art to have a BSI device that maintains the temperature of the device and the sample near or at a target temperature. Often, a BSI device utilizes a microfluidic chip to deliver the sample to a sensing area to be examined. Typically, the chip comprises channels of small dimensions, which can make it difficult for a user to interact with a chip and deliver a small sample to the chip. It would be desirable in the art to develop a microfluidic chip for use with BSI that can easily receive a sample from a user or sample delivery device, such as a pipette. The invention disclosed herein addresses some the issues in creating a reusable, stable interferometer.